Project Title - Social Influences on drug reward and monoamines: Adolescent social deprivation, social clues, and sex differences. Early life adversity, including adverse events that occur during adolescence, can produce vulnerability to, or conversely, resistance to drug addiction. Factors that may influence whether these events produce vulnerability or resistance to addiction include those related to the individual, such as its gender;the drug class involved, such as opioids or psychostimulants;and the context in which drug taking occurs. In social species including rats, adolescent social deprivation (isolation rearing) has been used as a model of adolescent adversity that produces changes in social behavior as well as alterations in the responses to drugs of abuse. Isolation rearing can produce a reduction in the rewarding properties of drugs of abuse, thus causing resistance to the intrinsic reinforcement dimension of addiction. Increasingly, social cues during drug exposure are recognized as an important component of the context in which drug exposure takes place. Social interactions can be highly rewarding, especially during adolescence, and social cues can potentiate the rewarding effects of drugs. Isolation rearing can produce an increase in the importance of social interactions, thus causing vulnerability to the social context dimension of addiction. Thus, isolation rearing may produce both vulnerability and resistance to drug addiction via effects on two different dimensions of drug exposure. Here it is predicted that the influence of social context on the rewarding effects of drugs will depend on the social history (social deprivation or social experience) of the individual during the critical period of adolescence. Moreover, sex differences in the responses to both isolation rearing and drug exposure are known to occur so and these effects may differ between males and females. The proposed research addresses these issues by asking the following questions: Do social cues during exposure to the opioid oxycodone or the psychostimulant cocaine have a greater impact on drug seeking behavior in male and female rats that have been socially deprived during adolescence? Is the mechanism of these effects related to changes in the neurochemistry of neural circuits involved in reward? These questions will be addressed in two specific aims. Specific Aim 1 is to determine the effects of isolation or group rearing on social cue-induced changes in drug- seeking behavior in male and female rats using conditioned place preference. Specific Aim 2 is to determine the effects of social cues during drug exposure on extracellular dopamine and serotonin in the nucleus accumbens and medial prefrontal cortex of isolation- or group-reared male and female rats using in vivo microdialysis. Understanding how drug and social rewards interact and how this may be mediated by the prior social experience and the sex of the individual can contribute to the development of interventions specific to at- risk individuals. PUBLIC HEALTH RELEVANCE: This proposal explores the role of social deprivation during adolescence on the impact of social cues on the rewarding properties and neurochemistry-altering properties of drugs of abuse, and asks whether this depends on the sex of the subject. The results have the potential to provide evidence that early adversity can interact with the drug-taking environment to influence the vulnerability to addiction, and may contribute to the development of interventions specific to at-risk individuals.